Specific Aims: 1. Determine the physiologic, metabolic and cerebrovascular responses of newborn dogs to graded doses of bacterial endotoxin. 2. Define the nature and time course of the neuropathologic injury induced by bacterial endotoxin and correlate the cerebral injury with the systemic alterations. 3. Determine the presumed beneficial effects of therapeutic agents in ameliorating the systemic and neuropathologic changes which occur during endotoxemia. 4. Assess the effect of endotoxin on the integrity of the blood-brain-barrier. Methods: 1. Measure regional cerebral blood flow (14C-iodoantipyrine method), glucose and lactate concentrations, blood pressure, pH, pO2 and pCO2 during graded endotoxemia in the newborn dogs. 2. Determine the neuropathologic effects of endotoxin in newborn dogs (by light microscopic techniques). 3. Assess the physiologic, metabolic and pathologic alterations in endotoxin exposed newborn dogs who are pre-tested with glucose, antibiotics and corticosteroids. 4. Determine the effect of endotoxin on the blood-brain-barrier utilizing Evans blue dye and 125I techniques. Objectives: Bacterial infections are a major cause of brain damage in the perinatal period and are of concern to pediatricians, neurologists and obstetricians. Although bacterial endotoxin is known to cause neuropathologic injury, the pathogenetic mechanisms are unknown. This proposal will elucidate the physiologic, metabolic and pathologic changes which occur during neonatal endotoxemia, and evaluate the potentially modifying effects of currently used therapeutic agents.